Project Summary/Abstract While cigarette use has declined in the US, use of electronic cigarettes (e-cigs) has increased dramatically since their introduction to the US in 2007. Tremendous controversy has emerged regarding their potential risks (renormalizing smoking, dangers of e-liquids) versus potential for harm reduction (?clean? nicotine delivery sys- tem without tobacco combustion products). The question of risks vs harm reduction is even more salient during pregnancy due to impact of maternal use on both mother and fetus and evidence for vulnerabil- ity of the developing fetus to both nicotine and combustion products. Recent published reports reveal rates of e-cig use of 4-15% among pregnant women; pilot data from our group revealed doubling of prenatal e- cig use between 2012 and 2017. Given evidence of increasing e-cig use by pregnant women, known fetal tox- icity from nicotine, and a need for data to inform pregnant women and obstetric providers, research to deter- mine the impact and relative impact (vs cigarettes) of e-cigs on fetal development is urgently needed. To date, however, there are no published studies of the impact of e-cig use during pregnancy on fetal develop- ment. We propose the first study of the impact of e-cigs during pregnancy on the developing fetus, in- cluding markers of fetal growth and novel measures of fetal brain and neurobehavioral development. Our group pioneered combined use of real-time ultrasound and fetal actocardiography to characterize fetal neurobehavior. The advent of 3D ultrasound offers higher resolution fetal images and allows volumetric char- acterization of specific fetal brain structures. Seminal preliminary data from our group highlights feasibility of recruiting pregnant e-cig users as well as initial evidence for alterations in fetal growth, fetal fronto-cerebellar brain structures and fetal neurobehavioral development in e-cig users. The proposed study is an intensive pro- spective investigation of three groups of mother-fetus pairs: E-cig users, Cig users and Controls. Comprehen- sive measures of fetal growth, neural structures, and neurobehavioral development will be assessed over preg- nancy using 2D and 3D ultrasonography followed by neonatal ultrasound and neurobehavioral assessment. Maternal and fetal nicotine, combustion and carcinogenicity biomarkers will also be assessed. Our goals are to determine the impact of prenatal e-cigs on: (1) fetal growth and infant birth weight, (2) fetal/infant brain devel- opment, (3) fetal/infant neurobehavioral development. We will also explore: (4) associations between nicotine and toxicity biomarkers with fetal growth, brain and neurobehavioral development. The proposed study ad- dresses an urgent and unanswered public health question. Given increasing rates of e-cig use and the exquis- ite sensitivity of the developing fetus to disruptions in the prenatal environment, determining the risks and rela- tive risks of e-cig use in pregnancy is timely and offers potential to impact the health of reproductive age women and their children.